title: miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer.
abstract: BACKGROUND
  Aquaporin-3 (AQP3) is a water transporting protein which plays an oncogenic role in several malignant tumors. However, its regulatory mechanism remains elusive to date. In this study, we investigated the microRNA-mediated gene repression mechanism involved in AQP3's role.
  
  
  METHODS
  The potential microRNAs targeting AQP3 were searched via bioinformatic methods and identified by luciferase reporter assays, microRNA RT-PCR and western blotting. The expression patterns of miR-874 and AQP3 in human gastric cancer (GC) specimens and cell lines were determined by microRNA RT-PCR and western blotting. 5-ethynyl-2'-deoxyuridine, cell migration and invasion assays and tumorigenicity in vivo were adopted to observe the effects of miR-874 depletion or ectopic miR-874 expression on GC cell phenotypes. Cell apoptosis was evaluated by FACS and TUNEL in vitro and in vivo respectively.
  
  
  RESULTS
  miR-874 suppressed AQP3 expression by binding to the 3'UTR of AQP3 mRNA in GC cells. miR-874 was significantly down-regulated and reversely correlated with AQP3 protein levels in clinical samples. Analysis of the clinicopathological significance showed that miR-874 and AQP3 were closely correlated with GC characteristics. Functional analyses indicated that ectopic miR-874 expression suppressed the growth, migration, invasion and tumorigenicity of GC cells, whereas miR-874 knockdown promoted these phenotypes. Down-regulation of Bcl-2, MT1-MMP, MMP-2 and MMP-9 and upregulation of caspase-3 activity and Bax were involved in miR-874 inducing cell apoptosis, and inhibiting migration and invasion.
  
  
  CONCLUSIONS
  These results provide a mechanism by which AQP3 is upregulated, as well as highlight the importance of miR-874 in gastric cancer development and progression.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Baofei
authors.initials: B
authors.lastname: Jiang
authors.forename: Zengliang
authors.initials: Z
authors.lastname: Li
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Haixiao
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhi
authors.forename: Jin
authors.initials: J
authors.lastname: Feng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051400:Aquaporin 3 / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002681:China; D003857:Deoxyuridine / Q000031:analogs & derivatives; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: C561946:MIRN874 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051400:Aquaporin 3; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine